Search

. Hepatitis delta virus (HDV) coinfection or superinfection in hepatitis B virus (HBV)-infected patients results in a more aggressive liver disease, with more often fulminant forms and more rapid progression to cirrhosis and hepatocellular carcinoma. The mechanism(s) for this pejorative evolution remains unclear. To explore a specific HDV pathogenesis, we used a model of transient transfection of plasmids expressing the small (sHDAg or p24) or the large (LHDAg or p27) delta antigen in hepatocyte cell lines. We found that the production of reactive oxygen species was significantly higher in cells expressing p27. Consequently, p27 activated the signal transducer and activator of transcription-3 (STAT-3) and the nuclear factor kappa B (NF-κB) via the oxidative stress pathway. Moreover in the presence of antioxidants (PDTC, NAC) or calcium inhibitors (TMB-8, BAPTA-AM, Ruthenium Red), p27-induced activation of STAT-3 and NF-κB was dramatically reduced. Similarly, using a mutated form of p27, where the cysteine 211-isoprenylation residue was replaced by a serine, a significant reduction of STAT-3 and NF-κB activation was seen, suggesting the involvement of isoprenylation in this process. Additionally, we show that p27 is able to induce oxidative stress through activation of NADPH oxidase-4. These results provide insight into the mechanisms by which p27 can alter intracellular events relevant to HDV-related liver pathogenesis. [ABSTRACT FROM AUTHOR]

Summary. Liver steatosis is a main histopathological feature of Hepatitis C (HCV) infection because of genotype 3. Steatosis and/or mechanisms underlying steatogenesis can contribute to hepatocarcinogenesis. The aim of this retrospective study was to assess the impact of infection with HCV genotype 3 on hepatocellular carcinoma (HCC) occurrence in patients with ongoing HCV cirrhosis. Three hundred and fifty-three consecutive patients (193 men, mean age 58 ± 13 years), with histologically proven HCV cirrhosis and persistent viral replication prospectively followed and screened for HCC between 1994 and 2007. Log-rank test and Cox model were used to compare the actuarial incidence of HCC between genotype subgroups. The patients infected with a genotype 3 ( n = 25) as compared with those infected with other genotypes ( n = 328) had a lower prothrombin activity [78 (interquartile range 60-85) vs 84 (71-195) %, P = 0.03] and higher rate of alcohol abuse (48% vs 29%, P = 0.046). During a median follow-up of 5.54 years [2.9-8.6], 11/25 patients (44%) and 87/328 patients (26%) with a genotype 3 and non-3 genotype, respectively, develop a HCC. HCC incidences were significantly different among the genotype subgroups ( P = 0.001). The 5-year occurrence rate of HCC was 34% (95% CI, 1.3-6.3) and 17% (95% CI, 5.7-9.2) in genotype 3 and non-3 genotype groups, respectively ( P = 0.002). In multivariate analysis, infection with a genotype 3 was independently associated with an increased risk of HCC occurrence [hazard ratio 3.54 (95% CI, 1.84-6.81), P = 0.0002], even after adjustment for prothrombin activity and alcohol abuse [3.58 (1.80-7.13); P = 0.003]. For patients with HCV cirrhosis and ongoing infection, infection with genotype 3 is independently associated with an increased risk of HCC development. [ABSTRACT FROM AUTHOR]

Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. Bulevirtide (BLV, Hepcludex ® ) is an HDV/HBV entry inhibitor approved in June 2020 in the European Union for adult patients with chronic hepatitis delta (CHD) and compensated liver disease and positive HDV RNA viral load. This real-life preliminary report described early virological efficacy and safety of BLV in six patients with CHD and compensated liver disease: four patients were treated with the combination of BLV (2 mg/d in subcutaneous injection) and pegylated interferon (PEG-IFN) and two patients with BLV monotherapy. Four patients treated with combined therapy had a decline of a minimum of 1 log 10 and 3/3 of 2 log 10 of HDV-VL at 12 and 24 weeks, respectively. One patient among four had stopped the treatment at 12 weeks because of thrombocytopenia and an HDV-VL relapse was notified 24 weeks after treatment cessation. Three patients among four (3/4) had undetectable HDV-VL during the therapy (<100 IU/ml). One patient (1/2) treated with BLV monotherapy had a decline of HDV-VL by 1 log 10 at 8 weeks and 1/1 by 2 log 10 at 28 week on-treatment. Two patients among four (2/4) with combined therapy had normal ALT reached at 4 and 56 weeks. One patient (1/2) with BLV monotherapy achieves ALT normalization at​ 4 weeks on treatment. Hepatitis B surface antigen (HBsAg) levels remain unchanged. Three among six (3/6) patients had an elevation of total biliary acids without pruritus. These early data generated confirm the interest in this new treatment. Final results will be important to demonstrate long-term clinical benefit (fibrosis reversibility and reduction in hepato-cellular carcinoma [HCC])., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: Hepatitis D virus (HDV) infection is associated with a more severe outcome in patients with chronic hepatitis B (CHB); however, little is known about the presence of HDV in sub-Saharan Africa. We aimed to determine the prevalence of HDV infection, as well as its clinical, biological and virological characteristics, in a large CHB cohort in Ethiopia., Methods: In total, 1267 HIV-negative CHB patients at St. Paul's Hospital Millennium Medical College in Addis Ababa were screened for anti-HDV antibodies using ELISA assays. Confirmed positive samples were further tested for HDV RNA using a consensus commercial real-time RT-PCR assay. HDV genotypes were also determined for RNA-positive samples by nucleotide sequencing followed by phylogenetic analyses. Demographical, clinical and biological data from patients were recorded and compared based on HDV RNA results., Results: Most patients (n = 748, 59.0%) were men, and the median age was 31 years (interquartile range 26-40). Anti-HDV antibodies were detected in 19 individuals (1.5%), 12 of whom were HDV RNA-positive with a viral load ranging from <2 to >8 log 10 IU/mL. All strains were genotype 1. HDV RNA-positive patients were more likely to have significant liver fibrosis (63.6% vs 24.7%, P = .007) and cirrhosis (45.5% vs 16.4%, P = .024)., Conclusions: HDV infection is rare in Ethiopia but is associated with more advanced liver fibrosis., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: Hepatitis B Virus (HBV) DNA during chronic infection can reach levels at which mother-to-child (MTC) transmission frequently occurs despite passive-active immunization of newborns. Hepatitis D Virus (HDV) RNA can reach high levels, we assessed HBV/HDV MTC co-transmission., Methods: Monocentric retrospective study (registered in ClinicalTrials.gov (NCT02044055)), after informed consent in HBV/HDV co-infected women pregnant between 01/01/2004 and 01/01/2015 in Paris, France. The children were tested when 24 months of age or older., Results: Twenty-two (3%) of 742 HBV infected women, HDV co-infected, gave birth to 54 children during the study period. HBV DNA was above 5 Log 10 I.U/mL in 10 pregnancies previous any treatment, with HDV RNA of less than 2.3 Log 10 I.U/mL. HDV RNA was above 5 Log 10 I.U/mL in eight pregnancies previous any treatment, with HBV DNA of less than 1.5 Log 10 I.U/mL. Inverse patterns of HBV DNA and HDV RNA were observed in 17 of 35 (49%) pregnancies: 13 (76%) received no HBV treatment; four (24%) were treated. HBV DNA was under 5 Log 10 I.U/mL in 46 of the 50 assessed women (92%) at birth. Of the 36 assessed children, given passive-active immunization, 24 (66%) were protected, 10 (28%) were neither infected nor protected, one was chronically HBV infected, and one had a past HBV infection. HDV Ab was negative in the 36 children., Conclusions: These results suggest that HBV/HDV MTC co-transmission is exceptional. Studies are needed, mainly in developing countries., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)